Sleep Architecture, Obstructive Sleep Apnea, and Cognitive Function in Adults

This cohort study investigates the association of sleep architecture and obstructive sleep apnea measures with cognitive function among middle-aged to older adults in 5 cohorts.


eMethods: The Sleep and Dementia Consortium (SDC): Design and Aims
The SDC curates data from 5 community-based cohorts that have performed methodologically consistent, overnight, home-based polysomnography (PSG) and neurocognitive assessments. The cohorts include the Atherosclerosis Risk in interactions (e.g., with the APOE genotype). Overall, the SDC aims to investigate sleep, cognition, and dementia risk comprehensively. Although this paper focuses on cognitive outcomes, other outcomes described in these eMethods will be examined in the future (e.g., risk of dementia).

Enrolment and cohort design methods
ARIC is a large, prospective study ongoing since 1987. ARIC was established to study cardiovascular disease in men and women from four geographically and racially diverse US communities: Minneapolis, MN; Washington County, MD; Forsyth County, NC; and Jackson, MS. A total of 15,792 participants (72% Whites) aged 45 to 64 years were enrolled at the baseline exam. PSGs were performed on a subset of participants from the Washington County, MD and suburban Minneapolis, MN sites. Participants are followed continuously for hospitalizations and death, and brief cognitive assessments were conducted at clinic visits 2 (1990-1992) and 4 (1996-1998). Between 2011 and 2013, all surviving ARIC participants were invited to complete a comprehensive dementia assessment (ARIC Neurocognitive Study) as part of the 5 th clinic visit, and a subset underwent MRIs. Since then, dementia surveillance has included annual administration of the six-item screener and when appropriate, the Alzheimer's Disease 8 scale with informants. Additionally, comprehensive dementia ascertainment has been repeated at 2 in-person visits (visit lists. An African-American cohort of 256 men and 431 women was added in 1992 from three of the four communities. Three of the four clinical centers participated in the SHHS (PA, CA, and MD). Persons were examined annually from enrolment to 1999 and continue to be monitored for morbidity and mortality. Annual exams have included a 30-minute screening cognitive battery. In 1992-94 and again in 1997-99, participants were invited to undergo brain MRI and detailed cognitive assessment (also performed annually thereafter) as part of the CHS Cognition Study.
FHS is an ongoing, longitudinal, community-based cohort study initiated in 1948 to investigate risk factors for CVD. The FHS now comprises three generations of participants: the Original cohort (Gen 1) followed since 1948, their Offspring (Gen 2) and spouses of these offspring, followed since 1971, and children from the largest Offspring families (Gen 3) enrolled in 2002. 1,2 The Gen 2 cohort of 5,124 persons has been examined every four years. A multi-ethnic cohort of racially diverse adults was recruited in 1994-98 (Omni 1, N=507) and tested in parallel with the Gen 2 cohort. PSGs were performed on a subset of Gen 2 and Omni 1. From 1999, all surviving participants were invited to undergo brain MRI, with cognitive testing available from an earlier time point. Surveillance for dementia is ongoing, and decisions on dementia diagnosis and subtype are made at a consensus review that considers FHS neurologist exams, family interviews, and brain autopsy data.

Assessment of brain MRI
Brain volumes on MRI are available for ARIC, CHS, and FHS. The acquisition and reading protocols have been described and harmonized previously as part of genetic consortia. 5,6 All MRI scans were obtained using 1.5 or 3T field strength machines. The sequences include T1-weighted and either FLAIR or T2-weighted and T2 susceptibility-weighted imaging or T2-weighted gradient-recalled echo. Diffusion Tensor Imaging is also available within ARIC and the FHS, albeit over 10 years after the initial sleep study (a mean of 16 years for ARIC and 16.9 years for FHS).

Overview of the sleep and brain health measures available across SDC
cohorts. All cohorts except SOF underwent polysomnography (PSG1 and 2) at two time points (only the first PSG and cognitive data is used in the current paper).

Race and ethnicity demographics
Query: For the SOF cohort: Race (which included Hispanic) was asked at the baseline SOF visit (1986)(1987)(1988), then at SOF visit 6 (1996-1998) a black cohort was added. The data used in this paper is from SOF visit 8 (2002-2004)  Multiracial and multiethnic categories: In some cases, it was possible for participants to select multiple categories or to select multiracial as a response to 'other.' For ARIC, Multiracial or multicultural is not relevant, since categories were mutually exclusive.    Description: Interaction between OSA and ESS scores in the FHS. There was a significant interaction between moderate to severe OSA (versus none) and excessive daytime sleepiness (ESS≥11) when predicting global cognition in the FHS. When stratifying by daytime sleepiness, prevalent moderate to severe OSA (vs. none) was associated with poorer the global cognition in persons with ESS scores ≥11 (β±SE= -0.536±0.215, p = 0.014). There was a no association between prevalent moderate to severe OSA and global cognition in persons with ESS scores <11 (β±SE = 0.160±0.108, p = 0.138).
Interaction between N2% and ESS scores in SOF. There was a significant interaction between N2 % and excessive daytime sleepiness (ESS≥11) when predicting global cognition in the SOF. When stratifying by daytime sleepiness, higher N2 % was associated with poorer the global cognition in persons with ESS scores ≥11 (β±SE = -10.77±4.76, p = 0.428), although the association did not reach statistical significance. In contrast, higher N2% was associated with better global cognition in persons with ESS scores <11 (β±SE = 0.805±0.620, p = 0.196).